Neurodegenerative Disorders

Cayman Chemical offers a broad collection of tools to study the mechanisms underlying various neurodegenerative disorders. This includes key compounds, peptides, antibodies, and assay kits used to research the disease pathways of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), muscular dystrophy, Huntington’s disease, and prion diseases.

Amyotrophic Lateral Sclerosis Prion Diseases Motor cortex, brainstem, spinal cord Cerebral cortex · Loss of motor neurons · PrP accumulation

Alzheimer’s Disease Huntington’s Disease Temporoparietal cortex Striatum · Aβ plaques · Hyperphosphorylated tau · Loss of medium spiny neurons · Mutant huntingtin aggregates

Muscular Dystrophy Cerebral cortex, thalamus, hippocampus, Parkinson’s Disease cerebellum, brainstem Midbrain substantia nigra, basal ganglia · Dystrophin deficiency · Loss of dopaminergic neurons · Myelin abnormalities · α-Synuclein toxicity

Alzheimer’s Disease Cayman offers compounds that target amyloid-β (Aβ) peptide production and aggregation, prevent tau protein phosphorylation and modification, and block cholinesterase (AChE and BChE) activity and excessive glutamate excitotoxicity. Amyloid-β Antibody, Peptides, and Fluorescent Probes Item No. Product Name Summary

11610 Amyloid-β Monoclonal Antibody (Clone 6C3, MOAB-2) Host: Mouse · Species Reactivity: (+) Human · Applications: ELISA, ICC, IP, WB

10229 Amyloid-β (1-8, A2V) Peptide Model peptide (dominant negative mutant) for design of amyloid formation inhibitors

20574 Amyloid-β (1-42) Peptide A 42-residue Aβ protein fragment

21617 Amyloid-β (1-40) Peptide (human) A 40-residue Aβ protein fragment

19814 CRANAD 2 A near-infrared Aβ fluorescent probe (Kd = 38 nM)

20476 Methoxy-X04 A brain-permeable fluorescent probe for Aβ

18520 NIAD-4 A fluorescent probe for Aβ (Ki = 10 nM) View additional inhibitors of Aβ at www.caymanchem.com

2019 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM BACE and γ-Secretase Inhibitors Item No. Product Name Summary Reduces BACE transcription and diminishes Aβ production, lowering the amount of Aβ1-40 and 11001 (R,S)-Anatabine Aβ1-42 in SHSY-5Y cells

14000 Auraptene Inhibits BACE1 activity (IC50 = 345.1 μM) Inhibits γ-secretase, blocking the cleavage of both APP and Notch carboxyl-terminal fragments 15579 Compound E (IC50s = ~0.3 nM) Inhibits γ-secretase, blocking the production of total Aβ and Aβ42 in human primary neuronal 13197 DAPT cultures (IC50s = 115 and 200 nM, respectively) Inhibits dipeptidic γ-secretase, demonstrating anti-Alzheimer activity in an APP transgenic 14627 DBZ mouse model by reducing Aβ40 levels

21599 LY2886721 Selectively inhibits BACE (IC50 = 20 nM for recombinant hBACE1) View additional inhibitors of BACE and γ-Secretase at www.caymanchem.com Tau Phosphorylation Inhibitors Item No. Product Name Summary Inhibits hippocampal tau phosphorylation and reverses cognitive deficits induced by the NMDA 16676 AZD 1080 receptor antagonist (+)-MK-801 (Item No. 10009019) Inhibits GSK3α and GSK3β (IC s = 0.65 and 0.58 nM, respectively), reducing tau 15578 CHIR98014 50 phosphorylation in rat brains

396 14704 GSK3β Inhibitor VIII Inhibits tau phosphorylation (IC50 = 2.7 μM) at a GSK3-specific site (Ser ) in cells

13314 Indirubin-3'-monoxime Inhibits GSK3β (IC50 = 22 nM), preventing tau phosphorylation

13237 Thiamet G Selectively inhibits O-GlcNAcase (Ki = 21 nM) and blocks phosphorylation of tau protein

Glutamate and Acetylcholine Signaling Inhibitors Item No. Product Name Summary Reversibly inhibits AChE which readily crosses the blood-brain barrier to reduce the breakdown of 13245 Donepezil acetylcholine

14184 Memantine (hydrochloride) Blocks the NMDA open-channel (Ki = 1.2 μM at -60 mV); uncompetitive antagonist

14270 Rivastigmine (tartrate) Irreversibly inhibits AChE and BChE (IC50s = 4.15 μM and 37 nM, respectively)

70240 Tacrine (hydrochloride) Inhibits both AChE and BChE (IC50s = 31 and 26.5 nM, respectively) Parkinson’s Disease Cayman offers dopamine-sparing compounds, anticholinergics, sirtuin inhibitors, and blockers of mutant leucine-rich repeat kinase 2 (LRRK2) all of which have been identified as therapeutic strategies to address the decline of dopamine-generating cells in the substantia nigra. Dopamine-Sparing Compounds and Anticholinergics Item No. Product Name Summary

16094 (−)-Apomorphine (hydrochloride) A non-selective dopamine receptor agonist with anti-parkinsonian and neuroprotective actions A centrally acting M mAChR antagonist (K = 0.59 nM in rat); inhibits dopamine uptake through 16214 Benztropine (mesylate) 1 i the dopamine transporter (Ki = 160 nM) 13248 L-DOPA A metabolic precursor of dopamine that crosses the blood-brain barrier A peripherally acting COMT inhibitor (K = 145 nM); decreases 3-OMD levels in rat brain and 14153 Entacapone i prolongs L-DOPA bioavailability 15622 GBR 12909 (hydrochloride) A dopamine uptake inhibitor in vivo, leading to consequent stimulation of dopamine receptors

17422 Raclopride A selective dopamine D2 and D3 receptor antagonist (Kis = 1.8 and 3.5 nM, respectively)

11982 SB 277011A (hydrochloride) A selective dopamine D3 receptor antagonist (pKi = 8.0)

15631 SCH 23390 (hydrochloride) A selective dopamine D1 and D5 receptor antagonist (Kis = 0.2 and 0.3 nM, respectively)

View additional dopamine-sparing compounds and anticholinergics at www.caymanchem.com

2019 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM α-Synuclein Toxicity Inhibitors Item No. Product Name Summary

13145 AGK2 Selectively inhibits SIRT2 (IC50 = 3.5 μM); rescues dopamine neurons from α-synuclein toxicity An aldehyde product of the oxidative deamination of dopamine by MAO that can oligomerize and 16214 Benztropine (mesylate) precipitate α-synuclein 15046 R-(−)-Deprenyl (hydrochloride) Prevents apoptosis induced by α-synuclein

LRRK2 Inhibitors Item No. Product Name Summary

14052 Diapocynin Reverses motor coordination deficits in the LRRK2R1441G mouse model of early Parkinson's disease

14603 GSK2578215A Inhibits both wild-type and G2019S mutant of LRRK2 (IC50s = 8.9 and 10.1 nM, respectively) A selective LRRK2 inhibitor (IC s = 2.2, 6.6, and 47.7 nM for G2019S-mutant, wild-type, and 22905 JH-II-127 50 A2016T-mutant LRRK2, respectively)

18094 LRRK2-IN-1 Inhibits both wild-type and G2019S-mutant LRRK2 (IC50s = 13 and 6 nM, respectively) Amyotrophic Lateral Sclerosis (ALS) Cayman offers a select group of assay kits, antibodies, and inhibitors to study many of the targets identified as potential factors leading to the development of ALS. This includes inhibitors of NADPH oxidase and superoxide dismutase (SOD), as well as antagonists of prostaglandin D2 (PGD2) and glutamate receptors. Inhibitors and Antagonists Item No. Product Name Summary

14321 AEBSF (hydrochloride) Prevents the activation of NADPH oxidase, an enzyme involved in ALS

11976 Apocynin Inhibits the assembly of a functional NADPH oxidase complex

14832 Ibudilast Inhibits PDE4 (IC50 = 54-239 nM), suppressing elaboration of mediators involved in inflammation Selective DP receptor antagonist (K = 0.57 nM); blocking PGD and its receptor activity may be 10009835 MK-0524 1 i 2 protective for motor neuron survival Blocks presynaptic release of glutamate, indirectly antagonizing glutamate receptors and 14577 Riluzole (hydrochloride) + inactivating neuronal voltage-gated Na channels (ED50 = 2.3 μM) SOD Antibodies Assay Kits Item No. Product Name Item No. Product Name

10011388 Cu/Zn SOD (human) Polyclonal Antibody 512031 Prostaglandin D2 ELISA Kit

10011387 Cu/Zn SOD (rat) Polyclonal Antibody 706002 Superoxide Dismutase Assay Kit

View additional assay kits at www.caymanchem.com Muscular Dystrophy

Cayman offers small molecules to study dystrophin deficiency and the disruption of abnormal PGD2 production via hematopoietic prostaglandin D synthase (H-PGDS), which is thought to be related to the expansion of muscle necrosis. Recombinant PGDS proteins and assays are also available. Small Molecules Item No. Product Name Summary

20316 21-desacetyl Deflazacort Active glucocorticoid that demonstrates benefits in certain muscular dystrophies An orally bioavailable upregulator of utrophin gene transcription; increases muscle function in 20309 Ezutromid dystrophin-deficient mdx mice 10134 HQL-79 A selective inhibitor of H-PGDS Prostaglandin D Synthase (hematopoietic-type) 16256 A selective blocker of H-PGDS (IC s = 0.7 and 32 nM in enzyme and cellular assays, respectively) Inhibitor I 50

WWW.CAYMANCHEM.COM CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 2019 PGDS Proteins PGDS Assay Kits Item No. Product Name Item No. Product Name Prostaglandin D Synthase Prostaglandin D Synthase 10006593 10007684 (hematopoietic-type; human recombinant) (lipocalin-type; human) ELISA Kit Prostaglandin D Synthase Prostaglandin D Synthase (hematopoietic-type) FP-Based 10006788 600007 (lipocalin-type; human recombinant) Inhibitor Screening Assay Kit - Green View additional PGDS proteins at www.caymanchem.com Huntington’s Disease Cayman offers compounds to investigate polyglutamate expansion and the accumulation of mutant huntingtin protein, which is thought to lead to degeneration of neurons in the striatum. Small Molecules Item No. Product Name Summary

14004 AK-7 A SIRT2 inhibitor that diminishes neuronal cell death induced by mutant huntingtin fragment

21177 C2-8 Inhibits polyglutamine-aggregation in Huntington's disease An orally available tissue transglutaminase inhibitor that is neuroprotective in mouse models of 14882 Cystamine (hydrochloride) Huntington’s disease 16946 7,8-Dihydroxyflavone Improves motor function and extends survival in an animal model of Huntington’s disease

17729 Ferrostatin-1 Inhibits cell death in models of Huntington’s disease Prevents formation of huntingtin protein aggregates in the brain and reduces the cognitive 22942 PAOA deficits in the N171-82Q mouse model of Huntington’s disease Protective against behavioral and striatal oxidative damage by increasing the activity of 15043 Probucol glutathione peroxidase in an in vivo mouse model of Huntington’s disease 20380 Tetrabenazine A chorea modulator that inhibits vesicular monoamine transporter 2 Prion Disease Cayman offers antibodies for immunochemical detection of prion proteins (PrPs) as well as small molecules that can be used to study PrP aggregation and misfolding. Small Molecules Item No. Product Name Summary

c 10010740 CAY10550 Inhibits the accumulation of PrP (IC50 = 3 nM)

13533 E-64d Inhibits protease-resistant PrP accumulation in scrapie-infected neuroblastoma cells (IC50 = 0.5 µM)

16674 Flupirtine (maleate) Decreases neurotoxicity associated with prion disease

15041 Quinacrine (hydrochloride hydrate) Prevents misfolding of PrP (EC50 = 0.3 μM)

11190 Termitomycamide B Protects against ER stress-dependent cell death

11191 Termitomycamide E Protects against ER stress-dependent cell death

Antibodies Item No. Product Name Summary Prion Protein Monoclonal Antibody Host: Mouse · Species Reactivity: (+) Bovine, caprine, ovine; (-) Human, hamster 10009025 (Clone 2G11) Application: IHC Prion Protein Monoclonal Antibody Host: Mouse · Species Reactivity: (+) Ovine; (-) Human, bovine, mouse 10009035 (Clone BAR 224) Applications: EIA, FC, IHC, WB Prion Protein Monoclonal Antibody Host: Mouse · Species Reactivity: (+) Human, bovine, hamster, mouse, ovine 189720 (Clone SAF 32) Applications: EIA, FC, IHC, WB View additional PrP antibodies at www.caymanchem.com Manufactured by:

2019 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM